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Schizophrenia and Aging: Myths and Reality

Schizophrenia and Aging: Myths and Reality. Dilip V. Jeste, M.D. Estelle & Edgar Levi Chair in Aging, Director, Stein Institute for Research on Aging, Distinguished Professor of Psychiatry & Neurosciences, University of California, San Diego & VA San Diego Healthcare System.

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Schizophrenia and Aging: Myths and Reality

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  1. Schizophrenia and Aging:Myths and Reality Dilip V. Jeste, M.D. Estelle & Edgar Levi Chair in Aging, Director, Stein Institute for Research on Aging, Distinguished Professor of Psychiatry & Neurosciences,University of California, San Diego & VA San Diego Healthcare System

  2. Potential Conflicts of Interest • Donation of antipsychotic medications for an NIMH-funded RO1: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen • Consultant: Solvay/Wyeth, Otsuka, Bristol-Myers Squibb

  3. Self-Assessment Question 1Which of the following statements is true? A. Rate of age-related cognitive decline in late-onset schizophrenia does not differ from that in normal subjects. • Remission of schizophrenia in late life appears independent of age or chronicity of illness • Positive symptoms in late-onset schizophrenia are as prevalent as in early-onset schizophrenia. • Female gender is over-represented among patients with late-onset schizophrenia • All of the above

  4. Self-Assessment Question 2Compared to early-onset schizophrenia, which of the following is true of late-onset schizophrenia? • Negative symptoms are more severe • Paranoid subtype is more prevalent • A smaller percentage of patients have ever been married • All of the above • None of the above

  5. Self-Assessment Question 3Which of the following statements is true of neuropsychological findings in patients with late-onset schizophrenia? • A wide range of cognitive deficits have been reported • Compared to patients with early-onset schizophrenia, less severe deficits in learning and executive functions characterize patients with late-onset schizophrenia • The overall pattern of deficits is similar to that seen in early-onset schizophrenia • All of the above • None of the above

  6. Self-Assessment Question 4Which of the following is true regarding treatment of late-onset schizophrenia? • The cumulative incidence of tardive dyskinesia with conventional antipsychotics is low in elderly patients. • Risperidone has been shown to be superior to olanzapine in treating positive and negative symptoms of late-onset schizophrenia. • Cognitive Behavioral Social Skills Training has been shown to reduce delusions and hallucinations • All of the above • None of the above

  7. Self-Assessment Question 5Which of the following are long-term adverse effects of atypical antipsychotics? • Weight gain • Type 2 diabetes mellitus • Dyslipidemia • Increase in strokes and mortality in dementia patients • Any of the above

  8. Major Points • Schizophrenia can manifest for the first time after age 40 • Course of schizophrenia in late life is generally characterized by persistence of negative symptoms, absence of rapid cognitive decline, and modest improvement in positive symptoms • Very late-onset schizophrenia-like psychosis (with onset after age 60) is a heterogeneous syndrome that includes psychosis of dementia or of other medical conditions, substance use, or psychosis NOS • Other conditions in differential diagnosis include delusional disorder and psychosis associated with mood disorders • Treatment with atypical antipsychotics is associated with symptomatic improvement but also potentially hazardous metabolic side effects offset by lower rates of tardive dyskinesia and other extra-pyramidal symptoms • Psychosocial approaches have been shown to improve functioning and insight but not psychopathology in older patients with schizophrenia.

  9. OUTLINE • Introduction • Course of Schizophrenia in Late Life • Middle-Age-Onset Schizophrenia • Very Late-Onset Schizophrenia-like Psychosis • Pharmacologic & Psychosocial Treatments

  10. Estimated Numbers of People with Psychiatric Disorders in USA Age Group _ Jeste et al., Arch Gen Psychiatry, 1999

  11. UCSD Studies of Late-Life Schizophrenia • Over 1200 middle-aged and elderly patients with schizophrenia and related psychoses, and over 250 normal comparison subjects • Longitudinal follow-up with comprehensive clinical, neuropsychological, and functional evaluations

  12. Course of Schizophrenia in Late Life • Relatively stable and non-deteriorating course • Negative symptoms persist while positive symptoms show a modest improvement • The rate of age-related cognitive decline is similar in patients and normal subjects Jeste DV et al., Acta Psychiatrica Scand, 2003

  13. Correlations with Age in Schizophrenia Patients Aged 40-85 (N=192) Positive Symptoms: SAPS -0.19* Negative Symptoms: SANS -0.15 Daily Neuroleptic Dose: -0.31** Cognitive Impairment: DRS 0.21* *p<0.05; **p<0.01

  14. 3 2 1 .9 .8 Impairment on DRS (Log of Reflected Scores) .7 .6 .5 .4 .3 Controls, N = 114 .2 Patients, N = 129 30 40 50 60 70 80 90 Age (yrs) Zorrilla E, et al., Am J. Psychiatry, 2000

  15. Stability of Neuropsychological Performance GlobalNP T-Score Short Followup Long Followup (Heaton et al., Arch. Gen. Psychiatry, 2001)

  16. Remission of Schizophrenia:Earlier Studies • Reported rates of remission or recovery range from 3% to 68% • Variable use and definitions of terms: Cure, Recovery, Remission • Bias in sample selection • Inconsistent diagnostic criteria for schizophrenia • Subjective evaluations

  17. UCSD Criteria for Sustained Remission • Met DSM-IV criteria for schizophrenia in past, but not currently; • No hospitalization for last 5 years; • Living independently; and • Neuroleptic-free or on low dose of an antipsychotic Auslander L & Jeste DV, Am J Psychiatry, 2004

  18. Remission Study Conclusions • 8% of the older schizophrenia patients living in the community met criteria for persistent symptomatic remission • Remitted patients had somewhat impaired cognition & functioning suggesting that remission in schizophrenia may reflect a return to pre-morbid functioning rather than to “normal level”

  19. Predictors of Sustained Remission from the Literature • Social support • Greater cognitive / personality reserve • Early initiation of treatment • NOT age or duration of illness

  20. Late-Onset Schizophrenia: A Controversial Entity Age of onset and diagnosis of schizophrenia in USA: DSM-III (1980) DSM-III-R (1987) DSM-IV (1994) European terminology: Paranoia Paraphrenia Late paraphrenia

  21. Questions 1. Can schizophrenia manifest after age 45? If it can, 2. Why do these patients develop schizophrenia? and 3. What protects them from developing schizophrenia until late in life?

  22. Diagnosis DSM-III-R or DSM-IV diagnosis with SCID Age of onset of prodromal symptoms of schizophrenia Specific inclusion and exclusion criteria Diagnostic stability over follow-up period

  23. Patient Characteristics

  24. SAPS Subscale Scores * * * * * NC < EOS & MAOS (p < .05) Palmer B, et al., Harvard Review of Psychiatry, 2001

  25. SANS Subscale Scores # # * # # * * * * NC < EOS & MAOS (p < .05) # EOS > MAOS (p < .05) Palmer B, et al., Harvard Review of Psychiatry, 2001

  26. MAOS: Similarities with EOS (I) Clinical • Severity of positive symptoms • Family history of schizophrenia • Minor physical anomalies • Childhood maladjustment • Sensory impairment Jeste et al., Am Psychiatry, 1995; Am J Geriat Psychiatry, 1997

  27. Age of Onset of Schizophrenia by Gender (Age > 45) 30 Men (N = 149) 20 Women (N = 59) Percent 10 0 5 15 25 35 45 55 65+ Age of onset Kolmogorov-Smirnov pvalue < .0001 Lindamer et al., Psychopharm. Bull., 1997

  28. MAOS: Differences from EOS (I) Clinical • More common in women • Less severe negative symptoms • Mostly paranoid subtype • Greater % of patients ever married Jeste et al., Am J Psychiatry, 1995; Am J Geriat Psychiatry, 1997

  29. Psychosocial Factors • Premorbid Functioning: Suboptimal without being grossly psychopathological; Premorbid personality may show paranoid or schizoid traits but not disorder. • Psychosocial Stressors: Retirement, bereavement, financial loss, physical disability, etc. may serve as precipitants and/or maintainers of psychosis.

  30. Neuropsychological Assessment • Expanded Halstead-Reitan battery, Age-, gender-, and education-corrected, T-, and deficit-scores for 7 ability areas: • Verbal, 2) Attention, 3) Psychomotor, • 4) Memory (retention), 5) Learning, • 6) Motor, and 7) Abstraction.

  31. Neuropsychological Deficit Scores *** *** *** * * p < .05; *** p < .0001(NC < MAOS, EOS)

  32. Neuropsychological Deficit Scores * * * *** *** *** * p .05; ***p<.0001 (NC < MAOS < EOS)

  33. MAOS (N=29) vs. Alzheimer Disease (N=61):Longitudinal Study of Mattis’Dementia Rating Scale (DRS) MAOS AD

  34. MAOS: Similarities with EOS (II) Neuropsychological (1) Overall pattern of cognitive impairment (III) MRI (1) Nonspecific MRI abnormalities (IV) Course & Treatment (1) Chronic Course (2) Qualitative response to neuroleptics (3) Increased mortality Jeste et al., Am J Psychiatry, 1995; Am J Geriatric Psychiatry, 1997

  35. MAOS: Differences from EOS (II) Neuropsychological (1) Less severe impairment in learning and in abstraction (III) MRI (1) Larger thalamus? (IV) Course & Treatment (1) Need for lower doses of neuroleptics Jeste et al., Am J Psychiatry, 1995; Am J Geriatric Psychiatry, 1997

  36. Very Late-Onset Schizophrenia-like Psychosis Heterogeneous group of disorders: • Psychosis of dementia • Psychosis secondary to general medical conditions or substance use • Mood disorder with psychotic features • Delusional disorder • Psychosis NOS Howard R et al., Am J Psychiatry, 2000

  37. International Consensus Statement on Late-Onset Schizophrenia In terms of epidemiology, symptomatology, and identified pathophysiology, LOS (onset after age 40) and very late-onset schizophrenia-like psychosis (onset after age 60) have face validity and clinical utility. • Howard, Rabins, Seeman, Jeste, and International LOS Group (representatives from Australia, Brazil, Canada, Denmark, France, India, Japan, Spain, Switzerland, UK and USA) American Journal of Psychiatry, 2000

  38. Cumulative Incidence of TD with Conventional Antipsychotics Kane et al., J Clin Psychopharm, 1988; Jeste et al., Am J Geriat Psychiatry, 1998

  39. Risperidone vs Olanzapine in Elderly Schizophrenia Pts. • International, double-blind, 8-week RCT* • 176 patients, aged >60 years • Schizophrenia or schizoaffective disorder • Randomly assigned to flexible doses of Risperidone (1-3; median 2 mg/d) or Olanzapine (5-20; median 10 mg/d) Jeste DV, et al., American Journal of Geriatric Psychiatry, 2003

  40. Risperidone Vs. Olanzapine • Both atypical antipsychotics produced significant improvement from baseline scores on PANSS • No significant difference between the 2 drugs on Psychopathology, Cognitive function, QTc, or Reports of EPS or anticholinergic side effects • Greater weight gain with olanzapine (p=.05) Jeste DV, et al., American Journal of Geriatric Psychiatry, 2003

  41. Percent with TD Haloperidol (N = 61) Risperidone (N = 61) Months Peto-Prentice p-value < .05 TD Incidence in Older Patients:Haloperidol versus Risperidone (1mg/d) Jeste, et al., JAGS, 1999

  42. Cumulative Incidence of Definitive TD in Older Patients With Borderline Dyskinesia % With Definitive TD * * P <.001 (Peto-Prentice) Dolder & Jeste. Biol Psychiatry. 2003, 53:1142-45

  43. Atypical Antipsychotics: Possible Long-Term Side Effects • Weight gain • Type 2 diabetes mellitus • Hyperlipidemia • Hyperprolactinemia • Cardiac conduction disorders • Strokes? • Increased mortality?

  44. FDA Warnings About Antipsychotic Use • In all age groups: Weight gain, Diabetes, Hyperlipidemia • In dementia patients: Strokes, and Mortality

  45. Caution in Interpreting Data on Strokes & Mortality with Antipsychotics • The patients in these trials were typically 80+ years old, and had multiple risk factors for strokes and mortality • No cause- and-effect relationship between the antipsychotics and these adverse events in individual patients has so far been clearly established • The exact underlying mechanisms are not yet known

  46. Drug Initial Typical Range Clozapine 6.25-12.5 50-150 Risperidone 0.25-0.5 1-3 Olanzapine 2.5-5 5-15 Quetiapine 12.5-25 75-200 Recommended Dosagesin Older Patients (mg/day)

  47. Other Atypical Antipsychotics • Ziprasidone • Aripiprazole • Others

  48. Psychosocial Tx of Late-Life Schizophrenia • Cognitive Behavior Therapy • Social Skills Training • Functional Adaptation Skills Training • Medication Adherence Therapy • Vocational Rehabilitation • Pedal for older Latino patients

  49. Cognitive Behavioral, Social Skills Training (CBSST) Three modules, each with 4 weekly sessions, to be repeated, for a total of 24 group sessions CBT – Thought challenging SST – Asking for support CBSST – Solving problems Manualized treatment, with homework assignment after “classes” Granholm E, et al., American Jr. of Psychiatry, 2005

  50. Randomized Controlled Trial of CBSST • 76 Patients with schizophrenia or schizoaffective disorder randomized to CBSST or Tx as usual • Blind assessments on Independent Living Skills Survey, Beck’s Cognitive Insight Scale, Comprehensive Module Test for CBSST skills, and Psychopathology (PANSS, HAM-D) at baseline, 3 months, & 6 months Granholm E, et al., American Jr. of Psychiatry, 2005

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